Two hypothalamic peptides with corticotropin releasing activity, vasopressin and the newly characterized 41 amino acid ovine CRF have been found in hypophysial portal blood at concentrations sufficient to stimulate ACTH secretion. The goal of the research described in this proposal is to elucidate the relative role of these peptides in the regulation of ACTH by simultaneously measuring the hypophysial portal plasma concentration of vasopressin and CRF under conditions associated with changes in ACTH secretion. Included in the experimental models to be studied are adrenalectomy, stress, and short and long loop feedback. The ability to now measure vasopressin and CRF in portal blood should make it possible to rapidly advance our knowledge of the CNS control of pituitary-adrenal function and should make a major contribution to the understanding of the homeostatic mechanisms involved in the response to stress.